A prospective analysis of bronchoalveolar lavage (BAL) in 13 patients with Wegener~s granulomatosis (WG), 20 disease control subjects with idiopathic pulmonary fibrosis (IPF), and 24 normal control subjects was conducted to evaluate the quality of the alveolar inflammatory response associated with active WG; determine whether antineutrophil cytoplasmic antibody (ANCA) is present in alveolar fluid and produced in the lungs of patients with WG; and determine whether inhaled particles or infectious agents may play an etiologic role in WG. BAL in untreated WG had a marked increase in neutrophils, and usually in eosinophils compared with that in normal controls, and untreated WG in remission. Disease controls with IPF, a process known to be associated with neutrophilic alveolitis, had an increased population of neutrophils and eosinophils in BAL. Leukocyte remnants and intact leukocytes, could be identified within BAL macrophages in the patients with WG and IPF, and rarely in the normal control subjects. Normal subjects and controls with IPF were negative for ANCA in serum, while ANCA was found in serum and BAL in all active WG patients with generalized disease. Protein analysis of BAL revealed a disproportionate increase in the IgG to albumin ratio compared with serum values (IgG index) in patients with active untreated disease, suggesting that IgG with ANCA reactivity is produced by pulmonary lymphoid tissue. No infectious agent in BAL was identified by the techniques applied in this study. If an infectious agent causes the neutrophilic alveolitis of active WG, its presence is either transient or it is not identifiable by most laboratory techniques. The neutrophilia in BAL of active WG contrasts with several other granulomatous lung diseases in which increased numbers of lymphocytes are noted. Observations of our controls show that phagocytosis of neutrophils by macrophages alone is not sufficient to lead to ANCA production, which distinguishes WG from other diseases that also have a neutrophilic alveolitis.